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Science 7 February 2003:
Vol. 299. no. 5608, pp. 887 - 890
DOI: 10.1126/science.1080280
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Reports

Myc-Induced T Cell Leukemia in Transgenic Zebrafish

David M. Langenau,1 David Traver,2 Adolfo A. Ferrando,1 Jeffery L. Kutok,3 Jon C. Aster,3 John P. Kanki,1 Shuo Lin,4 Ed Prochownik,5 Nikolaus S. Trede,2 Leonard I. Zon,2 A. Thomas Look1*

The zebrafish is an attractive model organism for studying cancer development because of its genetic accessibility. Here we describe the induction of clonally derived T cell acute lymphoblastic leukemia in transgenic zebrafish expressing mouse c-myc under control of the zebrafish Rag2 promoter. Visualization of leukemic cells expressing a chimeric transgene encoding Myc fused to green fluorescent protein (GFP) revealed that leukemias arose in the thymus, spread locally into gill arches and retro-orbital soft tissue, and then disseminated into skeletal muscle and abdominal organs. Leukemic cells homed back to the thymus in irradiated fish transplanted with GFP-labeled leukemic lymphoblasts. This transgenic model provides a platform for drug screens and for genetic screens aimed at identifying mutations that suppress or enhance c-myc- induced carcinogenesis.

1 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
2 Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
3 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
4 Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
5 Division of Hematology/Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.
*   To whom correspondence should be addressed. E-mail: thomas_look{at}dfci.harvard.edu

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